Ricki Lewis

Most of us have an intuitive understanding of how a vaccine works: show the immune system a bit of a pathogen, or something mimicking it, and trick it into responding as if natural infection is happening. The COVID-19 pandemic ushered in a flood of vaccine options.

When I was writing "How the various COVID vaccines work," which ran here at DNA Science on September 10, I had to keep reviewing summary charts to remember who was doing what. Vaccine technology has gone beyond live, weakened, or killed virus, even past the once-groundbreaking subunit vaccines that present parts of a pathogen, like the hepatitis B surface antigen or pertussis toxin. Now we have DNA and RNA vaccines too, delivered in different ways.

The first two vaccines against COVID-19, Tozinameran (the Pfizer/BioNTech vaccine) and mRNA-1273, Moderna's still unchristened candidate on the brink of emergency use authorization, are mRNA. And that's confusing people, based, perhaps, on when they took high school biology (more on that coming). So here's a brief consideration of mRNA and how it can alert the immune system to fight SARS-CoV-2.

To continue reading, go to my blog DNA Science at Public Library of Science.

The idea that old vaccines might have a role in the fight against COVID-19 has been floated since the early days of the pandemic. Vaccines stimulate the broad, innate immune response, which appears to play a key role in fighting COVID-19. Can the approach bridge the time until entire populations are vaccinated specifically against SARS-CoV-2?

Three vaccines dominate the discussion: bacillus Calmette-Guérin (BCG) against tuberculosis; measles, mumps, and rubella (MMR); and oral polio vaccine (OPV).

To continue reading, go to MedPage Today, where this article first appeared.

Early on in the pandemic, a worse clinical scenario for the male of the species emerged. A study published mid-May from Italian researchers offered early statistics from the WHO and Chinese scientists: a death rate of 1.7% for women and 2.8% for men. Then Hong Kong hospitals reported that 15% of females and 32% of males with COVID-19 needed intensive care or had died.

In July a Perspective published in Nature Reviews Immunology from researchers at Johns Hopkins University and the University of Montreal noted a similar "male bias" for other viral infections, including SARS and MERS. By then, the wide community testing in South Korea and data from the U.S. indicated 1.5-fold higher mortality for men for COVID-19. The pattern repeated in 38 countries, for patients of all ages.

Now a new study published in Nature Communications expands the increased risk for those who have only one X chromosome

To continue reading, go to my DNA Science blog at Public Library of Science.

It's hard to imagine anything worse than the horrors at our hospitals right now. But in a recent JAMA webinar, Nicholas Christakis, Yale Sterling Professor, put the fatality rate of COVID-19 into historical perspective:

"Bad as it is, the fatality rate, at .5-.8%, isn't as bad as bubonic plague, which would kill 50% of a population in a few months. Or Ebola at 80%. Or smallpox at 95%. It could have been so much worse." He's a physician, scientist, public health expert, and sociologist.

It's an unusual viewpoint to downplay the horror of this moment in time, but Dr. Christakis's new book, "Apollo's Arrow: The Profound and Enduring Impact of Coronavirus on the Way We Live," takes a broader look. He said at the webinar:

"This way we're living right now seems alien and unnatural, but plagues aren't new to our species, just new to us. People have struggled with plagues for thousands of years. The Iliad opens with a plague on the Greeks and Apollo reigns down, the Bible, Shakespeare. What's different about our current experience is our time in the crucible happens to be occurring when we can create a vaccine in real time. The fact that we have the technological capability to respond within a year with phase 3 trials of active agents is mind-boggling."

We aren't the only species subject to unseen pathogens, including the viruses that aren't even cells or technically alive, just borrowed bits of our own genomes turned against us. With Dr. Christakis's wider view in mind, I noticed a new article about an infectious cancer in Tasmanian devils. It combines two terrors.

A Transmissible Cancer

To continue reading, go to my blog DNA Science at Public Library of Science, where this post first appeared.

Science and medical writers have been under an avalanche of information for nearly a year now, as we translate technical information about COVID-19 for the public. Links to the latest journal articles overload our inboxes, but, at the beginning and now during another surge, tracking down experts to interview has been difficult. They're simply too busy saving lives.

A critical resource for me has been the series of JAMA Live Q+A webinars for the media hosted by Howard Bauchner, editor-in-chief of the Journal of the American Medical Association. It is wonderful to hear the top clinicians and researchers speak freely, at length, and in context, or meander – a nice contrast to the echoing soundbites of mainstream media.

JAMA webinar speakers have included the career scientists who've already led us through the waters of HIV/AIDS, hepatitis, influenza, Ebola, zika, SARS, and other epidemics and pandemics. Anthony Fauci is a frequent guest – I wrote up his talk with FDA's Peter Marks here.

The webinars also feature the young clinicians battling our new enemy. Early on, Maurizio Cecconi's session, "Coronavirus in Italy: Report From the Front Lines," brought me to tears. The head of the Anaesthesia and Intensive Care Department at Humanitas Research Hospital in Milan, Dr. Cecconi described, at the webinar and in a report (both accessible here), the admission of "patient zero" to the ICU in Lombardy, on February 20, 2020, and how his infection was traced to a local friend who'd had contact with an infected person from China. The 38-year-old was initially not very ill and partied a lot. And the rest is medical history.

Recently Dr. Bauchner spoke with Paul Offit, who directs the Vaccine Education Center and is an attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia. He's on the FDA Advisory panel that will meet December 10 to discuss Pfizer's COVID-19 vaccine and on the 17th to consider Moderna's.

Dr. Offit is best known for co-inventing a vaccine against rotavirus, a diarrheal disease that has claimed millions of lives. It became available in the US in 2006, and is on the World Health Organization's list of essential medicines. The clinical trials for the rotavirus vaccine RotaTeq took four years and involved 70,000 participants – much more typical than the lightning speed of the COVID vaccine trajectory.

Here's the Q+A from December 2, lightly edited, with my explanations in parentheses. I've omitted the discussion of who gets vaccine when – that's all over the news.

To continue reading, go to my blog DNA Science at Public Library of Science.

While antibodies have been the focus of testing for past infection with COVID-19, T cells will also provide some insights -- potentially better ones, experts say.

These lymphocytes are the first responders that then coordinate the immune response while building an imprint, a memory, so that subsequent infections fade quickly, often unnoticed.

T cell tests are more complex and typically reserved for research, but some may be coming to the clinic soon, with at least one company seeking FDA emergency use authorization (EUA). Recent studies indicate that assaying T cells can even improve diagnostic accuracy and possibly predict how COVID-19 will unfold.

"Testing T cell responses can accelerate detection of an infection by as much as a week. The cells come in on day 2 and they divide very quickly, to detectable levels as early as 3 or 4 days from infection," said Dawn Jelley-Gibbs, PhD, who investigated T cells in influenza at the Trudeau Institute in Saranac Lake, New York.

"Identifying people who have been infected and become immune could have huge benefits for enabling society to safely return to normalcy. Numerous antibody tests exist, but doubts remain about their reliability and about antibody longevity post-infection," said Maria Oliver, PhD, senior scientist at Indoor Biotechnologies in Great Britain, one of several companies developing clinical T cell tests.

T Cell Basics

To continue reading, please go to MEDPAGE TODAY, where this post first appeared.

Ominous headlines have been common in recent months declaring that antibodies against COVID-19 decline quickly. But the reports simply describe an expected phenomenon and are not evidence of waning immunity, experts say. And recent data show strong T-cell response in people who had mild or asymptomatic infections.

"A large number of investigators are reporting the antibody response in humans infected with COVID who recover tends to drop relatively quickly. To some people that's an alarm bell. Following recovery from an acute infection, a decline in antibodies is normal B-cell biology and is exactly what we predict," said Dan Barouch, MD, PhD, professor of medicine at Harvard Medical School in Boston, Massachusetts.

"Do titers stabilize? Do antibodies last a long time or not? It's an unknown area, but there are no alarm bells yet," Barouch told Medscape Medical News.

 
Researchers and clinicians use antibodies as a surrogate for an evolving adaptive immune response because they're far easier to assay than the T cells that drive the response and stimulate B cells to produce the antibodies.

In tracking the ups and downs of antibodies and T cells, researchers seek "correlates of protection." These are measurable signs that an individual is immune to a specific infection. For example, an antibody against the viral spike protein is a correlate of protection because it predicts neutralization of SARS-CoV-2.

The Immune Response to SARS-CoV-2

Both arms of adaptive immunity respond quickly to a viral infection. CD4 ("helper") T cells are activated by day 2 of infection and they stimulate B cells to make antibodies against the infective agent.

To continue reading go to Medscape Medical News, where this post first appeared.

My blog posts around Thanksgiving are predictably dull: Turkey Genetics 101, The Peaceable Genomes of Pumpkins.

But 2020 is like no other year. Humanity is at war with the novel coronavirus SARS-CoV-2.

Images of overwhelmed hospitals and mobile morgues that dominated reporting from New York City in March are now coming from everywhere.

A mutation that's entered the US a few times from Europe doubled transmission rate without affecting severity, which is one reason why the percentage of fatal cases has fallen. Still, it's a huge absolute number, because of the fact that nearly 12 million Americans (as of today) have been infected. More than a quarter of a million have died.

And yet, some people still deny reality. Nurses tell of patients on their deathbeds still insisting that the pandemic is a hoax, that they're suffering from something else.

A Dangerous Meme

To continue reading, please go to my blog DNA Science at Public Library of Science, where this post first appeared.

The components of certain things are meant to remain mysterious. The ingredients of sausage. A burger's slimy secret sauce. The recipe for Coke or Kentucky Fried Chicken.

Researchers from Stanford University are tackling the make-up of another entity, something rather new to our world: the stuff retrieved from swabs shoved up nostrils to sample genetic material from SARS-CoV-2, the virus behind COVID-19. A swab actually samples much more than the virus's RNA, required for diagnosis.

Super Swabs

John Gorzynski and colleagues describe the "multi-omic data repositories" from deployed swabs in a preprint (not yet peer-reviewed) and at the recent virtual annual meeting of The American Society of Human Genetics.

"A single nasopharyngeal swab can reveal substantial host and viral genomic information in a high-throughput manner that will facilitate public health pandemic tracking and research into the mechanisms underlying virus-host interactions," they write.

That's a mouthful. I'll just call them super swabs.

Amplifying Viral Sequences

Extracting clues from the stuff on the swabs is a little like collecting evidence at a crime scene. Several things happen.

To continue reading, please go to my blog DNA Science at Public Library of Science, where this post first appeared.

In the early weeks of the pandemic, as patients overwhelmed New York City hospitals, the clinical characteristics of the most vulnerable quickly became apparent: many of the sickest people were older or had "co-morbidities" like diabetes, hypertension, or respiratory conditions.

As weeks became months and the symptom spectrum widened and worsened, researchers began to focus on "host risk factors" to explain the increasingly apparent variability in the COVID-19 experience. According to Jack Kosmicki, PhD, of Regeneron Genetics Center, at the recent American Society of Human Genetics virtual annual meeting:

"Genetics is one avenue to better understand why outcomes of COVID are so different. Some patients have so few symptoms that they don't realize they're infected, yet the other end of the extreme is requiring hospitalization, or death. Genetic risk factors might influence the likelihood of becoming infected or requiring hospitalization."

So far, very few genes have been linked to COVID-19. Other factors like socioeconomic status, exposure to the virus in the workplace or in crowded housing conditions, being of Black or Asian ancestry and non-genetic pre-existing conditions are more important.

To continue reading, please go to Genetic Literacy Project, where this post first appeared.